A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Safety and Efficacy of Intravenous Iclaprim vs. Vancomycin in the Treatment of Acute Bacterial Skin and Skin Structure Infections Suspected or Confirmed to be Due to Gram-Positive Pathogens (REVIVE-1). (4th October 2017) - Huang, David
Abstract: Background: The objective of this study was to demonstrate the safety and efficacy of iclaprim, a new generation diaminopyrimidine, compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Methods: REVIVE-1 was a Phase 3, 600 patient double-blind, randomized (1:1), active-controlled, multinational trial in patients with ABSSSI. The safety and efficacy of iclaprim 80 mg was compared with vancomycin 15mg/kg. Both were administered intravenously every 12 hours for 5 to 14 days with the length of treatment dependent on investigator assessment of clinical response. The primary endpoint of this study was to determine whether iclaprim was non-inferior (NI; 10% margin) to vancomycin in achieving a ≥20% reduction in lesion size (early clinical response [ECR]) at 48 to 72 hours after initiation of the study drug (ETP) compared with baseline. A secondary endpoint of this study was to demonstrate that iclaprim was NI to vancomycin at the test of cure (TOC) visit, 7 to 14 days after the study drug completion. Results: Iclaprim achieved NI compared with vancomycin at both the ETP and at the TOC (Table below). 60.4% of patients receiving iclaprim demonstrated resolution or near-resolution at end of therapy (EOT), compared with 58.3% of patients receiving vancomycin (treatment difference: 2.07%, 95% CI: -5.80% to 9.94%). Using a modified clinical cure TOC endpoint defined by a ≥90% reduction in lesion size at TOC, no increase in lesion size since ETP and no requirement for additional antibiotics, clinical cure was seen in 68.5% of patients receiving iclaprim and 73.0% of patients receiving vancomycin (treatment difference: -4.54%, 95% CI: -11.83% to 2.74%). The rate of study drug-related treatment emergent adverse events was 19.5% and 17.8% for iclaprim and vancomycin, respectively. Conclusion: Iclaprim was safe and efficacious in this Phase 3 trial for the treatment of ABSSSI. It was well tolerated with a low rate of drug-related adverse events and met its primary endpoint of NI at ETP and at TOC. Based on these results, iclaprim appears to be a valuable treatment for ABSSSI suspected or confirmed to be due to Gram-positive pathogens. Disclosures: D. Huang, Motif Bio: Employee, Salary; R. Shukla, Motif Bio: Employee, Salary